tbuckley/cabot-search huggingface dataset:
RONC-08. Validation of Online Calculator for Estimating Severe Hearing Loss Risk Among Patients with Medulloblastoma After Receiving Photon Radiation and Cisplatin Chemotherapy
Authors: Mohammad Abu-Arja, Austin Brown, Philip Lupo, Murali Chintagumpala, Arnold Paulino
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Children with medulloblastoma are at risk of hearing loss (HL) following cranial radiotherapy and platinum-based chemotherapy. Keilty et al. 2021. J Clin Oncol. (PMID: 34570616) recently published a computer-based HL risk calculator based on children with central nervous system tumors treated with photon radiotherapy. The objective of this study was to evaluate the performance of the risk calculator in an independent cohort of children with medulloblastoma treated with photon radiotherapy. METHODS: We identified children with medulloblastoma treated with cisplatin and photon radiotherapy at Texas Children’s Hospital between 1997-2007. Audiograms were graded using the International Society of Pediatric Oncology-Boston scale (SIOP-Boston). The risk calculator considered age at treatment, time since radiotherapy, cumulative cisplatin dose (mg/m2), and cochlea radiation dose (Gy). The calculated risk was compared between ears with and without clinical evidence of grades 3/4 HL using t-test. RESULTS: We identified 45 eligible patients (male: 31, female: 14) diagnosed at a median age of nine years (range: 3-18 years). The mean cochlea dose was 37.2 Gy (range: 25.2-54.9 Gy) and mean cumulative cisplatin dose was 352 mg/m2 (range: 55-860 mg/m2). Audiograms of 89 total ears were available with a median follow-up of 65 months post-diagnosis (range: 13-163 months). The median number of post-radiotherapy audiograms per patient was 6 (range: 2-15). A total of 22 ears (25%) belonging to 13 individual patients (29%) met the SIOP-Boston criteria for grades 3/4 HL. The mean of predicted probability of severe HL based on the calculator for ears with SIOP-Boston grades 3/4 was 24% (range: 10% - 48%) compared to 32% (range: 10%-70%) among ears with grades &amp;lt; 3 HL. CONCLUSION: The published HL risk calculator did not clearly differentiate between patients with and without clinically significant HL in our cohort. Future multicenter studies are required to validate this tool and improve the prognostic potential.³
Use of RET inhibitors among patients with advanced NSCLC: A real-world evidence analysis.
Authors: Shaheenah S. Dawood, Kaylen Brzozowski
Journal: Journal of Clinical Oncology (2022)

9079 Background: RET rearrangements are found in approximately 1% to 2% of patients with NSCLC. Two selective RET inhibitors have been FDA approved based on phase 1/2 data showing significant activity among patients with advanced NSCLC that have RETrearrangements. The objective of this retrospective analysis was to look at the prognostic outcome associated with the use of selective RET inhibitors (sRETi) and multikinase inhibitors (MKIs) that have been used to target RET fusions among pts with NSCLC in the real-world setting. Methods: We utilized a federated network of de-identified health data representing approximately 84 million pt lives available through the TriNetX Research Network. We identified 1,215 pts with metastatic NSCLC treated with selpercatinib, praseltinib, cabozantanib or vandetanib. Overall survival (OS) was evaluated with Kaplan Meier statistics and compared between patients treated with either sRETi (selpercatinib or pralsetinib) vs either MKI (cabozantanib or vandetanib). Results: Mean age among all anti-RET treated patients was 67.6 years. 518 pts (43%) were female and 697 (57%) were male. 531 (39.6%), 205 (15.3%) and 605 (45.1%) pts had received selpercatinib, pralsetinib, and either cabozantinib or vandetinib, respectively. 56.6% of pts receiving pralsetinib received prior selpercatinib. Among pts receiving sRETi, 39.7%, 6.4%, 11.2%, and 32.4% received sRETi in the 0-3, 3-6, 6-12, and 12+ months after metastatic diagnosis, respectively. Among pts receiving MKIs, 17.0%, 8.4%, 13.3%, and 44.9% received MKIs in the 0-3, 3-6, 6-12, and 12+ months after metastatic diagnosis. Median OS after treatment with MKIs and sRETi during any time frame was 16.3m and 25.0m, respectively (p &lt; 0.01). Among pts treated with MKIs vs sRETi during the 0-3, 3-6, 6-12, and 12+ months after metastatic diagnosis, 1-year survival probability after treatment was 59.7% vs 55.9% (p = 0.39), 45.0% vs 83.1% (p &lt; 0.01), 53.9% vs 82.2% (p &lt; 0.01), and 57.7% vs 87.1% (p &lt; 0.01), respectively. 30% of pts of all anti-RET treated patients had brain metastases, and median OS from index metastasis among pts with and without brain metastases was 31.4m and 63.1m respectively (p &lt; 0.01). Conclusions: To our knowledge this is the first real world data set to show a &gt; 8m improvement in OS with the use of sRETi compared to MKIs among pts with metastatic NSCLC. OS improvements may be more significant in pts treated in later lines of therapy with sRETi.
MEDB-89. Elucidation of the Oncogenic role of Nuclear Factor I/B (NFIB) in group 3 medulloblastoma
Authors: Naveenkumar Perumal, Ranjana Kanchan, David Doss, Ishwor Thapa, Mohd W Nasser, Surinder Batra, Sidharth Mahapatra
Journal: Neuro-Oncology (2022)

Abstract Amongst the 4 subgroups of medulloblastoma (MB), tumors falling into group 3 are the most aggressive and associated with increased incidence of aberrations on chromosome 17p, c-Myc amplification, metastases at diagnosis, and rapid tumor relapse. Thus, patients with group 3 tumors suffer the worst prognosis with a 5-year survival rate of &amp;lt;50%. We have prior identified a novel tumor-suppressive microRNA, miR-212, silenced on chromosome 17p and its deregulated oncoprotein target, Nuclear Factor I/B (NFIB). Here, we sought to identify the role of NFIB in group 3 MB pathophysiology. NFIB is a transcription factor that regulates chromosomal gene accessibility and expression of pro-metastatic genes in various cancers. Transcriptomic interrogation of group 3 tumors revealed deregulated expression of NFIB. Kaplan-Meier survival analysis confirmed poorer survival in NFIB high-expressing patients. Using inducible silencing of NFIB in a classic group 3 MB cell line, HDMB03, we observed downregulation of key driver genes (49 genes, Log2 fold change &amp;lt; -0.5, p &amp;lt; 0.001) associated with group 3 MB pathogenesis by RNA sequencing. NFIB expression knockdown (NFIBKD) further reduced tumor cell growth and aggressiveness, as evidenced by reduced proliferation, colony formation, migration, and invasion. NFIBKD also affected group 3 MB stemness, with attenuation of medullospheres and a reduction in stem cell markers (Nanog, Oct4, Sox2, CD133). Moreover, NFIBKD destabilized c-Myc phosphorylation at serine-62, resulting in reduced total c-Myc levels and subsequent cellular apoptosis. Concurrently, NFIBKD decreased the expression of upstream activators of c-Myc such as p-Akt and p-Erk. Taken together, these results validate the oncogenic role of NFIB in group 3 medulloblastomas and provide a potential new therapeutic target.
COVID-19 impact on multiple myeloma prescribing patterns.
Authors: Elias Pittos, Dipti Shah, Kelly McAuliff, Amanda McCarthy, William Cavers, Rashmi Grover, Lucia Feczko, Elisea Avalos-Reyes, Kjel Andrew Johnson
Journal: Journal of Clinical Oncology (2022)

e20027 Background: COVID-19 has impacted several areas of oncology patient care, most notably the reduction of patient visits for treatments. Standard treatment of multiple myeloma (MM) involves a combination of intravenous (IV) and oral therapies. The purpose of this study is to assess the impact COVID-19 had on IV and oral medication prescribing patterns pre and during the COVID-19 pandemic among MM patients. Methods: This is a retrospective review of adult MM patients insured by a large commercial and Medicare health plan in the United States who started a new IV or oral MM agent during the study period. To assess the impact of COVID-19 on IV and oral medication prescribing patterns, we compareda pre-COVID period (March 1-August 31, 2019) to a COVID period (March 1-August 31, 2020). We utilized medical and pharmacy claims to identify patients and calculated new therapy starts per newly diagnosed patient (defined as the number of patients starting a new IV or oral medication for MM divided by the total number of patients with a first indication date of MM within the study timeframe). We compared rates using a Chi-square test; p-values ≤ 0.05 were considered statistically significant. Results: 1,754 patients were enrolled in the study; there were no significant differences in demographic characteristics pre and during COVID-19 between the two groups with respect to age (67.05 vs. 66.64; p=0.45), gender (p=0.80), insurance plan type (p=0.17), geographical region (p=0.26) and medication (p=0.59). During COVID-19, the number of newly diagnosed MM patients decreased by 22% (9,657 to 7,560) and the total number of new therapy starts decreased by 11% (930 to 824). When looking at rates of new therapy starts per newly diagnosed patient, both IV (11%; p=0.03) and oral (51%; p=0.03) medication rates significantly increased. Additionally, there were significant increases in new therapy start rates by region in the Northeast for oral (157%; p&lt;0.01) and West for IV (32%; p=0.02) medications. There were no significant differences in new start rates by insurance plan type (all p&gt;0.08). Conclusions: While the total count of new therapy starts, a proxy for new diagnoses, decreased during COVID-19, the rate of new starts for both IV and oral therapies for patients diagnosed with MM significantly increased. These increased start rates may be explained by a remarkable 22% drop in the total number of newly diagnosed MM patients during COVID-19. As the pandemic continues, further study is warranted to understand how COVID-19 may impact IV vs. oral usage in MM. [Table: see text]
Total cost of care differences in National Comprehensive Cancer Center (NCCN) concordant and non-concordant breast cancer patients.
Authors: Ujwal Sapkota, William Cavers, Shirisha Reddy, Elisea Avalos-Reyes, Kjel Andrew Johnson
Journal: Journal of Clinical Oncology (2022)

e18833 Background: National Comprehensive Cancer Network (NCCN) treatment guideline non-concordance for breast cancer treatment has higher total costs. However, a significant knowledge gap exists regarding which cost components increase in non-concordant therapies. The purpose of this study is to evaluate the total cost of care (TCOC) and cost components for breast cancer patients who received NCCN concordant versus non-concordant therapies. Methods: This is a retrospective study of patients throughout the United States with breast cancer at a large national Medicaid, Medicare, and commercial insurer from January 1, 2019, to December 31, 2020. NCCN regimen concordance was identified from pharmacy and medical claims and defined as concordant if the entire prescribed treatment regimen matched an NCCN regimen (Level 1 and 2a); patients not receiving an NCCN recommended regimen were deemed to be non-concordant. TCOC and its cost components were contrasted on a matched population of concordant and non-concordant patients with a ratio of 2:1. To eliminate possible selection bias and differences in baseline characteristics that could affect cost, propensity scores were developed using logistic regression and used to match patients on age, comorbidity, socioeconomic status (SES) index and treatment type (chemotherapy and radiation). Results: A total of 315 patients with breast cancer were matched. Beginning with and including the first treatment and for up to 180 days after, the TCOC in the concordant group was significantly less across all lines of business (p &lt; 0.05). A reduction of 25%, 28% and 43% (a difference of $5,872, $6,946 and $3,542) in TCOC per member per month (PMPM) was observed in commercial fully insured (CFI), commercial self-insured (CSI) and Medicare patients, respectively. Provider administered chemotherapy spend was also significantly lower (p &lt; 0.05) in the concordant group, a reduction of 34%, 50% and 43% (a difference of $3,615, $6,788 and $1,879) in CFI, CSI and Medicare patients, respectively. Outpatient spend was 28% lower (a difference of $4,268, p = 0.08) in CFI patients and significantly lower (p &lt; 0.05) with reductions of 29% and 40% ($5,396 and $1,988) in CSI and Medicare patients, respectively. There were no significant differences in Inpatient and Emergency Room spend across all lines of business (p &gt; 0.05). Conclusions: In this study, there is a correlation between breast cancer patients on NCCN concordant therapies and a lower TCOC. The savings due to medical spend highlight the importance of evidence-based guidelines in treatment determinations. Further evaluation will be needed to determine cost changes in hospitalizations and emergency room visits.
Signature based on B cells-related gene pairs could predict prognosis and immunotherapeutic response in NSCLC.
Authors: Xuanzong Li, Xinyu Fan, Linlin Wang
Journal: Journal of Clinical Oncology (2022)

e21051 Background: Tumor-infiltrating B cells accompanying several widely used B cell-related biomarkers, such as CD19 and CD20, have inconsistent clinical prognostic values in non-small-cell lung cancer (NSCLC) patients. Considering only one B cell-related biomarker could not distinguish the anti-tumor and pro-tumor B cell subsets in tumor, we aimed to construct a more accurate B-cells related gene pairs (BRGPs) prognostic model and evaluate its potential predictive ability to immunotherapy in NSCLC patients. Methods: Using public single-cell RNA sequencing data, the B cells-related genes (BRGs) in NSCLC samples were identified. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were utilized to construct the BRGPs model which was not affected by the technical bias of different platforms. With no dependence upon specific gene expression levels, a novel signature based on BRGPs was established in this study. In addition, the prognostic value and immunotherapeutic response for this signature with regard to the TME components and potential molecular mechanism were explored. Results: Based on the TCGA database, we built a novel prognostic signature of 23 BRGPs comprising 28 unique BRGs. This risk model showed significant power in distinguishing good or poor prognosis and could serve as an independent prognostic factor for NSCLC patients in the TCGA cohort. The prognostic accuracy of the model was further verified in the GSE31210 dataset from the GEO database. Likewise, the prognostic value of the risk score for the BRGPs model was demonstrated in the GEO cohorts by the univariate and multivariate cox regression analysis. In addition, the risk model was significantly associated with sex, TNM stage, immune score, tumor purity and various tumor-infiltrating immune cells. GSEA analysis indicated that low-risk group enriched with several immune-related pathways, such as activation of immune response, antigen receptor mediated signaling pathway, B cell activation and B cell mediated immunity, whereas several proliferation-related pathways, such as nuclear chromosome segregation, sister chromatid segregation and mitotic sister chromatid segregation were most enriched in high-risk group. Besides, the tumor mutational burden (TMB) score rather than CD274(PD-L1 mRNA) expression was positively correlated with the risk score (P＜0.001; P = 0.94, respectively). NSCLC patients with high-risk exhibited significantly higher TMB score compared with low-risk patients (P &lt; 0.001). Correspondingly, we demonstrated that immune checkpoint blockade therapy may be more efficacious in high-risk group NSCLC patients according to TIDE method (P＜0.01). Conclusions: This novel BRGPs model can assess the prognosis of patients with NSCLC, and may be helpful to guide immune checkpoint inhibitors treatment in our clinical practice.
DIPG-05. How do potassium channels contribute to the growth and invasion of highly-aggressive brain cancers?
Authors: Yasmin Boyle, Emily Fletcher, Terrance Johns
Journal: Neuro-Oncology (2022)

Abstract Glioblastoma (GBM) is a lethal form of high-grade glioma with a dismal median survival time of just 15 months. Characterised by its’ highly diffuse and intrinsic growth pattern, GBM invades the healthy brain at an alarming rate. While diffuse midline glioma (DMG) is a much rarer disease, it is even more lethal, with a 5-year survival rate of just 2%. Though GBM is largely diagnosed in adults, DMG primarily affects young children aged 5-9 years and accounts for 10% of all childhood CNS cancers. Thus, while rare, DMG is highly aggressive and currently has no effective treatments to extend survival times beyond the median of 9 months. There is a pressing need for the development of novel and improved targeted therapies for each of these devastating diseases. Ion channels have long been implicated in the progression of numerous cancer types, due to their integral roles in proliferation, cell cycle transition, apoptosis, migration, and cellular plasticity. Voltage-gated potassium channels (VGKCs), in particular, have strong links to the key processes of proliferation, migration and invasion in GBM tumours. Given that the majority of GBM-related deaths are attributed to secondary tumours and metastasis, targeting proteins that are integral to these processes could result in reduced recurrence. Preliminary evidence suggests a potential role for the VGKC subtypes Kv5.1, Kv7.2, and the Kv4 subfamily in GBM and DMG, due to observed upregulation of these genes in both patient-derived cell lines and tumour samples. These particular VGKC subtypes are highly novel with regards to these cancers, while their significant upregulation suggests they may be associated with tumour progression. Thus, we aim to further explore the relationship between ion channel function and tumourigenesis in GBM and DMG, with a specific focus on VGKC subtypes and their potential therapeutic value.
Early mortality in real-life nationwide epidemiological study on lung cancer in non-academic French public hospitals.
Authors: Didier Debieuvre, David Marquette, Jacky Crequit, Jacques Le Treut, Laurent Portel, Reda Chikouche, Hugues François, Charles Dayen, Claudia Rizzo, Eric Goarant, Amélie Turlotte, Baihas Jarjour, Philippe Masson, Mohamad Jaafar, Clothilde Marty, Luc Stoven, Laure Belmont, Christine Le Foll, David Renault
Journal: Journal of Clinical Oncology (2022)

10557 Background: Each decade since 2000, the French College of General Hospital Pulmonologists (CPHG) conducts a real-life nationwide prospective epidemiological, observational, multicenter study on lung cancer (LC). In 2020, the CPHG constituted the third cohort, KBP-2020-CPHG. We reported here the data on one-month and three-month mortality among general population of this cohort and compared them with 2010 cohort. Methods: Collection of all consecutive LC histologically or cytologically confirmed between 01/01 and 12/31/2020 in non-academic public hospital pulmonology or oncology units in France. A Scientific Committee controlled inclusion exhaustivity and quality in each center. Results: 82 centers collected 8,999 patients in 2020. One-month mortality was 8.8% (734/8,999) and 9.7% (680/7,051) in 2010. Three-month mortality was 21.5% (1,771/8,999) in 2020 and 23.3% (1,624/7,051) in 2010 (Table 1). According to sex, mortality at one and three months mainly affected men (525/734; 71.5% and 1,259/1,771; 71.1% respectively). Mean age at diagnosis was older than in the cohort population (67.8 y-o); respectively 69.9 and 69.8 at one and three months. At diagnosis, patients were in poorer ECOG mainly grade 2 (211/697; 30.3%) or 3 (194/697; 27.8%) for one-month and mainly grade 1 (549/1,703; 32.2%) or 2 (547/1,703; 32.1%) for three-month mortality. Among ECOG grade 3 and 4, 34.8% (194/557) and 57.1% (93/163) were dead at one month respectively; 63.5% (350/551) and 83.4% (136/163) respectively were dead at three months. According to histology, adenocarcinoma was the most common (308/734; 42%), followed by small cell lung cancer (170/734; 23.2%) at one-month; adenocarcinoma was also the most common (822/1,771; 46.4%), followed by squamous cell carcinoma (380/1771; 21.5%) at three-month mortality. Most patients who died early were stage 4, metastatic/disseminated (respectively 625/702; 89% and 1,488/1,715; 86.8% for one- and three-month mortality). In patients with COVID19 infection (n=547), mortality at one and three months was respectively 36.4% (174/478) and 46.7% (228/488). Conclusions: Early mortality has not improved over the two decades and remains high. KBP-2020-CPHG study was performed during COVID-19 pandemic, which may have generated delays in diagnosis and limited access to care and hospital. Early mortality at one and three months concerned mostly men, mean age nearly 70 y-o, adenocarcinoma, metastatic disease and frail patients. This confirms the potential value of LC screening program in a targeted population. [Table: see text]
T-cell infiltration in matched samples from malignant pleural mesothelioma (MPM) during evolution of disease.
Authors: Susana Cedres Perez, Garazi Serna, Juan David Assaf Pastrana, Patricia Iranzo, Ana Callejo, Nuria Pardo, Alejandro Navarro, Alex Martinez-Marti, Carlos Cabrera Galvez, Alberto Gonzalez-Medina, Roberta Fasani, Xavier Guardia, Javier Gonzalo, Caterina Carbonell, Joan Frigola, Ramon Amat, Ana Vivancos, Paolo Nuciforo, Enriqueta Felip
Journal: Journal of Clinical Oncology (2022)

e20595 Background: MPM is an aggressive cancer associated with asbestos exposure. Chemotherapy has been a mainstay of therapy and recently immunotherapy has been associated with survival improvements. Chemotherapy and immunotherapy influence the tumor microenvironment and some reports have shown increased of TIL after chemotherapy in MPM. The purpose of this study was to determine dynamic changes in the tumor immune environment during mesothelioma evolution and after systemic therapies in paired samples. Methods: We examined 20 matched formalin-fixed paraffin embedded tissue samples from 10 patients (p) with MPM taken at diagnosis and at disease progression (follow-up), including untreated and treated with chemotherapy or immunotherapy. Tissue densities (number of cells/mm2) of key immune effector cells such as total lymphocytes (CD3), cytotoxic T cells (CD8), regulatory T cells (FOXP3) and monocytes/macrophages (CD163) were quantified by image analysis using multiplexed immunohistochemistry (IHC). PD-L1 expression in both tumor cells and immune cells was analysed by singleplex IHC and quantified using the CPS score. Results: Median age was 62 years (range 53-84), 7 p were male and all p presented epithelioid histology. Three matched samples belong to patients that did not receive any systemic treatment between biopsies and the other 7 pair of samples belong to patients treated with chemotherapy +/- immunotherapy. The median interval between paired biopsies was 12 m (3-33 m). Median overall survival was 27.8 months (1 m-NR). Median densities of T cells and macrophages in diagnostic and matched follow-up samples were: CD3+:982 vs 712; CD8+:422 vs 334, FOXP3+: 22 vs 25 and CD163+: 2086 vs 1706. Median PD-L1 CPS was 2.5 and 4 in diagnostic and follow-up samples, respectively. In p receiving treatment between sample pairs, the median densities in diagnostic and follow-up matched samples were: CD3+:979 vs 407; CD8+:467 vs 225, FOXP3+: 25 vs 15, CD163+: 1583 vs 1508, and PD-L1: 2 and 1. In p without any systemic treatment between sample pairs, the median densities were CD3+:1645 vs 2397; CD8+:376 vs 1605, FOXP3+: 19 vs 121, CD163+: 2102 vs 2377, and PD-L1: 3 vs 25. Conclusions: In our small series with paired samples from MPM p, we observed immune cells infiltration changes during MPM evolution with a trend towards a decrease after systemic therapy. Further investigation in tumor microenvironment in MPM to define the most appropriate time for immunotherapy is needed.